The proposed study is directed toward evaluation of hematopoietic cellular proliferation in polycythemia vera and other myeloproliferative disorders. The studies include: 1) assay, biochemical separation and characterization of regulatory factors (stimulatory and inhibitory) present in serum and urine of patients with myeloproliferative disease by the study of their in vivo effect in adult mice and fetal sheep, as well as their influence on proliferation and differentiation of mouse, fetal sheep and human bone marrow cells in vitro; 2) evaluation of proliferative characteristics of erythroid and white blood cell precursor cells in these disorders by their ability to form erythroid and leukocytic colonies in vitro in the presence or absence of erythropoietin and colony stimulating factor; 3) separation and characterization of the erythroid precursor cell population from bone marrow of patients with polycythemia vera, with capabilities of erythroid colony formation in the absence of added erythropoietin, and comparison to the population of cells separated from fetal sheep bone marrow; 4) investigation of mechanisms (humoral or cell mediated) responsible for the change in the erythroid precursor cell population in fetal sheep from erythopoietin-independent activity in vitro to dependence upon added erythropoietin for erythroid colony formation; and 4) development of a more rapid and economical assay procedure for the myelostimulatory factor present in sera of patients with myeloproliferative disorders.